Hetero-Diels-Alder Reactions under Microwave Irradiation
J . Org. Chem., Vol. 64, No. 17, 1999 6305
the appearance of two yellow spots with Rf values of ∼0.5 and
∼0.4. After 6 h the solvent was evaporated, and cycloadducts
were isolated as described above.
1H), 5.50 (dd, J ) 10.3 Hz, 1.6 Hz, 1H), 5.23 (ddd, J ) 8.3 Hz,
6.6 Hz, 2.9 Hz, 1H), 4.85 (dd, J ) 10.3 Hz, 3.5 Hz, 1H), 4.36-
4.22 (m, 3H), 4.13-3.95 (m, 3H), 3.73 (s, 3H), 2.13 (s, 6H), 2.01
(s, 6H), 1.36 (t, J ) 7.1 Hz, 3H), 1.02 (t, J ) 7.1 Hz, 3H); 13C
NMR (CDCl3) δ 169.8, 169.2, 169.2, 155.5, 154.4, 138.4, 136.0,
127.7, 117.4, 113.2, 68.3, 67.7, 67.0, 63.8, 62.9, 61.9, 54.7, 50.4,
20.1, 20.0, 19.8, 19.8, 13.6, 13.3; HRMS found 624.2273
(C27H36N4O13 requires 624.2279), ∆ ) 0.9 ppm.
(6R)- a n d (6S)-6-(1′,2′,3′,4′-Tetr a -O-a cetyl-D-a r a bin o-
t et r it ol-1′-yl)-1,2-b is(et h oxyca r b on yl)-3-p h en yl-1,2,3,6-
tetr a h yd r o-1,2,3,4-tetr a zin es (7 a n d 11). These substances
were obtained as yellowish oils in 93% overall yield. The
diastereomeric ratio (85:15) was determined by 1H NMR
integration of the residue. Compound 7 had [R]D +333.5° (c
0.5, CHCl3); 1H NMR (CDCl3) δ 7.27 (m, 5H), 6.92 (d, J ) 3.5
Hz, 1H), 5.64 (dd, J ) 8.1 Hz, 1.7 Hz, 1H), 5.52 (dd, J ) 10.2
Hz, 1.7 Hz, 1H), 5.23 (m, 1H), 4.83 (dd, J ) 10.2 Hz, 3.5 Hz,
1H), 4.38-4.02 (m, 6H), 2.16 (s, 6H), 2.05 (s, 6H), 1.26 (t, J )
7.1 Hz, 3H), 1.09 (t, J ) 7.1 Hz, 3H); 13C NMR (CDCl3) δ 170.4,
169.7, 169.7, 169.6, 154.8, 144.4, 135.1, 128.5, 122.4, 115.0,
69.0, 68.3, 67.5, 64.4, 63.6, 62.4, 51.1, 20.7, 20.6, 20.5, 20.4,
14.0, 13.8; HRMS found 594.2147 (C26H34N4O12 requires
594.2173), ∆ ) 4.3 ppm. Compound 11: [R]D -165.6° (c 0.5,
(6R)- a n d (6S)-6-(1′,2′,3′,4′-Tetr a -O-a cetyl-D-lyxo-tetr i-
tol-1′-yl)-1,2-bis(eth oxycar bon yl)-3-ph en yl-1,2,3,6-tetr ah y-
d r o-1,2,3,4-tetr a zin es (15 a n d 16). These diastereomers
were isolated in 91% overall yield (dr ) 66:33). Compound
15: crystals from benzene, mp 140 °C, [R]D +414° (c 0.5,
1
CHCl3); H NMR (CDCl3) δ 7.29 (m, 4H), 7.17 (d, J ) 3.5 Hz,
1H), 7.00 (m, 1H), 5.58 (t, J ) 4.6 Hz, 1H), 5.47 (m, 1H), 5.36
(dd, J ) 4.1 Hz, 3.1 Hz, 1H), 4.98 (t, J ) 3.1 Hz, 1H), 4.31 (dd,
J ) 12.0 Hz, 4.7 Hz, 1H), 4.24-4.10 (m, 5H), 2.16 (s, 3H), 2.11
(s, 3H), 2.08 (s, 3H), 2.02 (s, 3H), 1.24 (t, J ) 7.1 Hz, 3H), 1.18
(t, J ) 7.1 Hz, 3H); 13C NMR (CDCl3) δ 170.3, 169.9, 169.4,
169.2, 154.3, 154.0, 144.6, 136.4, 128.6, 122.5, 114.9, 72.9, 69.8,
68.6, 64.1, 63.4, 61.6, 52.5, 20.7, 20.6, 20.5, 14.0, 14.0. Anal.
Calcd for C26H34N4O12: C, 52.51; H, 5.76; N, 9.42. Found: C,
52.51; H, 5.90; N, 9.49.
1
CHCl3); H NMR (CDCl3) δ 7.30 (m, 5H), 7.01 (d, J ) 3.0 Hz,
1H), 5.75 (dd, J ) 6.5 Hz, 5.1 Hz, 1H), 5.48 (dd, J ) 6.5 Hz,
4.6 Hz, 1H), 5.36 (m, 1H), 4.99 (dd, J ) 4.6 Hz, 3.0 Hz, 1H),
4.44 (dd, J ) 11.5 Hz, 3.7 Hz, 1 H), 4.35-4.10 (m, 5H), 2.10
(s, 6H), 2.07 (s, 6H), 1.26 (t, J ) 7.0 Hz, 3H), 1.16 (t, J ) 7.0
Hz, 3H); 13C NMR (CDCl3) δ 170.4, 169.6, 169.4, 155.5, 153.5,
145.0, 134.1, 128.6, 122.5, 115.0, 70.0, 69.2, 63.9, 63.7, 61.3,
53.1, 20.6, 20.5, 14.2, 14.0.
Compound 16: [R]D -403.2° (c 0.5, CHCl3); 1H NMR (CDCl3)
δ 7.31-7.21 (m, 4H), 7.02-6.94 (m, 1H), 6.91 (d, J ) 3.7 Hz,
1H), 5.74 (bs, 1H), 5.52 (dd, J ) 10.2 Hz, 2.8 Hz, 1H), 5.35
(ddd, J ) 8.1 Hz, 4.0 Hz, 1.5 Hz, 1H), 4.95 (t, J ) 3.4 Hz, 1H),
4.40 (dd, J ) 11.8 Hz, 4.0 Hz, 1H), 4.37 (bs, 2H), 4.13-3.95
(m, 2H), 3.81 (bs, 1H), 2.16 (s, 3H), 2.08 (s, 3H), 2.01 (s, 3H),
1.99 (s, 3H), 1.46 (bs, 3H), 1.08 (t, J ) 7.1 Hz, 3H); 13C NMR
(CDCl3) δ 170.3, 170.2, 169.7, 169.4, 155.6, 153.5, 144.6, 134.3,
128.6, 122.4, 115.0, 68.1, 68.0, 67.6, 63.8, 63.7, 62.9, 52.6, 20.8,
20.6, 20.5, 14.2, 13.8.
(6R)- a n d (6S)-6-(1′,2′,3′-Tr i-O-a cetyl-D-er yth r o-tr itol-1′-
yl)-3-(4-b r om op h en yl)-1,2-b is(et h oxyca r b on yl)-1,2,3,6-
tetr a h yd r o-1,2,3,4-tetr a zin es (17 a n d 18). Diastereomers
were isolated in 80% overall yield (dr ) 35:65). Compound
17: Crystals from ether-hexane, mp 132 °C, [R]D +408° (c
0.5, CHCl3); 1H NMR (CDCl3) δ 7.37 (d, J ) 9.0 Hz, 2H), 7.13
(d, J ) 9.0 Hz, 2H), 6.94 (d, J ) 3.6 Hz, 1H), 5.59 (dd, J )
10.1 Hz, 2.6 Hz, 1H), 5.51 (m, 1H), 4.99 (dd, J ) 3.6 Hz, 2.6
Hz, 1H), 4.50-4.20 (m, 4H), 4.18-4.01 (m, 2H), 2.12 (s, 3H),
2.05 (s, 3H), 2.01 (s, 3H), 1.37 (t, J ) 7.0 Hz, 3H), 1.14 (t, J )
7.1 Hz, 3H); 13C NMR (CDCl3) δ 170.2, 169.4, 168.9, 155.0,
153.1, 143.4, 135.0, 131.3, 116.2, 114.6, 68.2, 67.5, 63.7, 63.6,
(6R)- a n d (6S)-6-(1′,2′,3′,4′-Tetr a -O-a cetyl-D-a r a bin o-
tetr itol-1′-yl)-3-(4-ch lor op h en yl)-1,2-bis(eth oxyca r bon yl)-
1,2,3,6-tetr a h yd r o-1,2,3,4-tetr a zin es (8 a n d 12). These
diastereomers were obtained in 96% overall yield (dr ) 84:
16). Compound 8 was crystallized from ether and had mp 112
1
°C, [R]D +381.5° (c 0.5, CHCl3); H NMR (CDCl3) δ 7.22 (m,
4H), 6.90 (d, J ) 3.5 Hz, 1H), 5.63 (dd, J ) 8.2 Hz, 1.9 Hz,
1H), 5.50 (dd, J ) 10.1 Hz, 1.9 Hz, 1H), 5.23 (ddd, J ) 8.2 Hz,
6.6 Hz, 2.9 Hz, 1H), 4.82 (dd, J ) 10.1 Hz, 3.5 Hz, 1H), 4.43-
4.23 (m, 3H), 4.15-4.01 (m, 3H), 2.16 (s, 3H), 2.15 (s, 3H), 2.05
(s, 6H), 1.33 (t, J ) 7.1 Hz, 3H), 1.13 (t, J ) 7.1 Hz, 3H); 13C
NMR (CDCl3) δ 170.5, 169.8, 169.7, 169.7, 154.8, 154.7, 143.1,
135.5, 128.6, 127.5, 116.1, 69.0, 68.3, 67.6, 64.7, 63.9, 62.5, 51.2,
20.8, 20.7, 20.7, 20.6, 14.1, 14.0; HRMS found 628.1781 (C26H33
ClN4O12 requires 628.1783), ∆ ) 0.4 ppm. Anal. Calcd for
26H33ClN4O12: C, 49.65; H, 5.24; N, 8.90. Found: C, 49.58;
-
C
H, 5.22; N, 8.83.
Compound 12: yellow oil, [R]D -174° (c 0.5, CHCl3); 1H NMR
(CDCl3) δ 7.22 (m, 4H), 7.00 (d, J ) 3.2 Hz, 1H), 5.74 (dd, J )
6.4 Hz, 4.9 Hz, 1H), 5.48 (dd, J ) 6.4 Hz, 4.5 Hz, 1H), 5.36 (m,
1H), 4.99 (m, 1H), 4.48-4.07 (m, 6H), 2.11 (s, 3H), 2.09 (s, 3H),
2.04 (s, 3H), 2.03 (s, 3H), 1.38-1.13 (m, 6H); 13C NMR (CDCl3)
δ 170.5, 169.6, 169.4, 169.4, 155.4, 153.3, 143.1, 134.4, 128.6,
127.5, 116.1, 70.1, 70.0, 69.3, 64.1, 63.9, 61.3, 53.1, 20.7, 20.6,
20.5, 14.2, 14.0.
61.0, 52.7, 20.7, 20.3, 14.0, 13.8; HRMS found 600.1063 (C23H29
BrN4O10 requires 600.1067), ∆ ) 0.8 ppm. Anal. Calcd for
23H29BrN4O10: C, 45.93; H, 4.91; N, 9.32. Found: C, 45.93;
-
C
H, 4.92; N, 9.24.
Compound 18: [R]D -361° (c 0.5, CHCl3); 1H NMR (CDCl3)
δ 7.39 (d, J ) 9.0 Hz, 2H), 7.18 (d, J ) 9.0 Hz, 2H), 7.15 (d, J
) 3.4 Hz, 1H), 5.49 (dt, J ) 6.1 Hz, 3.9 Hz, 1H), 5.38 (t, J )
3.9 Hz, 1H), 4.94 (dd, J ) 3.9 Hz, 3.4 Hz, 1H), 4.45 (dd, J )
12.2 Hz, 3.9 Hz, 1H), 4.33 (dd, J ) 12.2 Hz, 6.1 Hz, 1H), 4.28-
4.13 (m, 4H), 2.13 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H), 1.35-1.19
(m, 6H); 13C NMR (CDCl3) δ 170.0, 169.2, 169.0, 154.0, 153.7,
143.5, 136.5, 131.3, 116.1, 114.6, 72.8, 69.9, 64.2, 63.3, 61.4,
52.1, 20.5, 20.3, 13.9, 13.8.
(6R)-6-(1′,2′,3′,4′-Tet r a -O-a cet yl-D-a r a bin o-t et r it ol-1′-
yl)-1,2-b is(et h oxyca r b on yl)-3-(4-m et h ylp h en yl)-1,2,3,6-
tetr a h yd r o-1,2,3,4-tetr a zin e (9). This compound was iso-
1
lated as an oil in 87% yield: [R]D +422.3° (c 0.5, CHCl3); H
NMR (CDCl3) δ 7.16 (d, J ) 8.6 Hz, 2H), 7.07 (d, J ) 8.6 Hz,
2H), 6.91 (d, J ) 3.6 Hz, 1H), 5.63 (dd, J ) 8.2 Hz, 1.7 Hz,
1H), 5.50 (dd, J ) 10.2 Hz, 1.7 Hz, 1H), 5.23 (ddd, J ) 8.2 Hz,
6.7 Hz, 2.9 Hz, 1H), 4.85 (dd, J ) 10.2 Hz, 3.6 Hz, 1H), 4.40-
4.00 (m, 6H), 2.29 (s, 3H), 2.15 (s, 3H), 2.14 (s, 3H), 2.04 (s,
6H), 1.34 (t, J ) 7.1 Hz, 3H), 1.08 (t, J ) 7.1 Hz, 3H); 13C
NMR (CDCl3) δ 170.4, 169.7, 169.7, 169.6, 154.8, 142.4, 135.0,
132.0, 129.0, 115.4, 68.9, 68.3, 67.5, 64.4, 63.5, 62.4, 51.0, 20.8,
20.7, 20.6, 20.5, 20.4, 14.1, 13.8; HRMS found 608.2330
(C27H36N4O12 requires 608.2329), ∆ ) 0.2 ppm.
Ack n ow led gm en t. We gratefully acknowledge the
financial support of the Direccio´n General de Investi-
gacio´n Cient´ıfica y Te´cnica, Spain (PB95-0259) and the
J unta de Extremadura-Fondo Social Europeo (PRI97-
C175). One of us (F.R.C.) thanks the Spanish Ministerio
de Educacio´n y Cultura for a fellowship. The authors
also thank members of the technical departments of
Merck and Prolabo, Spain, for providing assistance with
the focused microwave reactor.
(6R)-6-(1′,2′,3′,4′-Tet r a -O-a cet yl-D-a r a bin o-t et r it ol-1′-
yl)-1,2-bis(eth oxyca r bon yl)-3-(4-m eth oxyp h en yl)-1,2,3,6-
tetr a h yd r o-1,2,3,4-tetr a zin e (10). This diastereomer was
1
isolated as an oil in 92% yield: [R]D +417° (c 0.5, CHCl3); H
NMR (CDCl3) δ 7.19 (d, J ) 8.8 Hz, 2H), 7.01 (d, J ) 3.5 Hz,
1H), 6.83 (d, J ) 8.8 Hz, 2H), 5.67 (dd, J ) 8.3 Hz, 1.6 Hz,
J O990442X